Projects. Life and Matter Sciences

Astrocytes: new anti-epileptic targets in Lafora disease.

Lafora disease (LD) is rare recessive neurological disorder with a prevalence of less than 1<1.000.000 inhabitants. It is characterized by neurodegeneration, progressive myoclonus epilepsy and accumulation of poorly branched glycogen-like deposits in brain and other peripheral tissues named Lafora bodies (LBs). All these hallmarks lead to the death of the patient around ten years after the appearance of the first symptoms. In spite of the excellent recent discoveries, the actual molecular bases of the disease are still poorly understood. At present, patients are treated initially with a combination of the regular antiepileptic drugs, which although they result effective in the first stages of the disease, they become completely useless in more advanced states. Therefore, there is no treatment yet for this devastating disease. In the present project we propose to gain knowledge on the dysfunctions present in astrocytes from mouse models of Lafora disease, with the aim to identify novel therapeutic targets that could benefit the disease. Our hypothesis is based on several results that indicate that Lafora disease presents a general metabolic dysfunction (i.e., accumulation of LBs, higher sensitivity to endoplasmic reticulum stress, oxidative stress, alterations in protein turnover and degradation, reactive astrogliosis, release of pro-inflammatory mediators, etc.). In our opinion, this energetic dysfunction severely affects astrocyte functionality, and as a consequence, the function of the surrounding neurons with which they interact. We think that an improvement in astrocyte functionality will lead to a better neuronal function and this will result in an amelioration of the neurological symptoms present in LD.